The human T-cell leukemia virus (HTLV) is associated with leukemia and neurological syndromes. The role of viral envelopes in HTLV physiopathology is unclear and the envelope receptor, found in all vertebrate cell lines, remains unidentified.
HTLV envelope glycoproteins induce syncytium formation in vitro but their physiopathological effects are unclear. All vertebrate cell lines express functional HTLV envelope receptors, including cells resistant to HTLV envelope-mediated syncytium formation.
The Applicant found that expression of the HTLV receptor-binding domain decreased lactate production due to diminished glucose consumption whereas binding-defective envelope mutants did not alter glucose metabolism. Glucose starvation increased HTLV receptor expression, reminiscent of nutrient sensing responses. Accordingly, overexpression of Glucose Transporter 1 (GLUT1), the ubiquitous vertebrate glucose transporter, specifically increased HTLV envelope binding and GLUT1 colocalized with HTLV envelopes. Moreover, HTLV envelope binding was highest in human erythrocytes, where GLUT1 is abundantly expressed and is the sole glucose transporter isoform.
In the present invention, the Applicant identified specific fragments of PTLV envelope protein that bind to GLUT1.